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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02967692




Registration number
NCT02967692
Ethics application status
Date submitted
16/11/2016
Date registered
18/11/2016
Date last updated
14/04/2021

Titles & IDs
Public title
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
Scientific title
A Randomized, Double-blind, Placebo-controlled, Phase III Study Comparing the Combination of PDR001, Dabrafenib and Trametinib Versus Placebo, Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Secondary ID [1] 0 0
2016-002794-35
Secondary ID [2] 0 0
CPDR001F2301
Universal Trial Number (UTN)
Trial acronym
COMBI-i
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Spartalizumab (PDR001)
Other interventions - Placebo
Treatment: Drugs - Dabrafenib
Treatment: Drugs - Trametinib

Experimental: Investigational treatment arm - Part 1: Safety run-in Up to 18 evaluable patients with previously untreated unresectable or metastatic BRAF V600 mutated melanoma will be enrolled and treated at different dose levels to determine the recommended Phase 3 regimen of PDR001 in combination with dabrafenib and trametinib.
Part 2: Biomarker cohort Approximately 20 patients with previously unresectable or metastatic BRAF V600 mutated melanoma will be enrolled to describe changes in the immune microenvironment and biomarker modulations
Part 3: Randomized double blind Approximately 500 patients with previously untreated unresectable and metastatic BRAF V600 mutated melanoma will be enrolled to compare the anti-tumor activity of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib.

Placebo Comparator: Placebo comparator arm - Matching placebo in combination with dabrafenib and trametinib


Other interventions: Spartalizumab (PDR001)
Spartalizumab (PDR001) will be supplied in vial in liquid or lyophilized pharmaceutical form. Spartalizumab (PDR001) will be administered via intravenous infusion over 30 minutes (up to 2 hours) once every 4 or 8 weeks.

Other interventions: Placebo
Placebo will be a Dextrose 5% in water (D5W) infusion supplied by the site.

Treatment: Drugs: Dabrafenib
Dabrafenib will be provided by the sponsor to the investigative site or supplied locally as commercially available. Dabrafenib will be administered orally twice daily (150 mg BID) for Days 1-28 of a 28-day cycle.

Treatment: Drugs: Trametinib
Trametinib will be provided by the sponsor to the investigative site or supplied locally as commercially available. Trametinib will be administered orally once daily (2 mg QD) for Days 1-28 of a 28-day cycle.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run-In (Part 1): Incidence of dose limiting toxicities (DLTs) - Incidence of DLTs during the first 8 weeks of treatment with Spartalizumab (PDR001) in combination of dabrafenib and trametinib
Timepoint [1] 0 0
8 weeks
Primary outcome [2] 0 0
Biomarker cohort (Part 2): Immune microenvironment and biomarker modulation - Changes in PD-L1 levels and CD8+ cells upon treatment with Spartalizumab (PDR001) in combination with dabrafenib and trametinib
Timepoint [2] 0 0
2 years
Primary outcome [3] 0 0
Randomized (Part 3): Progression-Free Survival (PFS), investigator assessed by RECIST 1.1 - Progression-free survival is defined as the time from the date of first dose to the date of the first documented radiological progression using RECIST 1.1 response criteria
Timepoint [3] 0 0
Up to disease progression or death due to any cause, whichever occurs first (5 years)
Secondary outcome [1] 0 0
Overall survival - Overall survival is defined as the time from date of randomization to date of death due to any cause
Timepoint [1] 0 0
Up to death due to any cause (5 years)
Secondary outcome [2] 0 0
Overall response rate - ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1
Timepoint [2] 0 0
Up to disease progression or death due to any cause, whichever occurs first (5 years)
Secondary outcome [3] 0 0
Duration of response - Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria
Timepoint [3] 0 0
Up to disease progression or death due to any cause, whichever occurs first (5 years)
Secondary outcome [4] 0 0
Disease control rate - Disease control rate is defined as the proportion of patients with CR or PR or subjects with SD lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria
Timepoint [4] 0 0
Up to disease progression or death due to any cause, whichever occurs first (5 years)
Secondary outcome [5] 0 0
Global health status/quality of life score of the EORTC QLQ-C30 - Patient's health-related quality of life
Timepoint [5] 0 0
Up to 60 days post progression (5 years)
Secondary outcome [6] 0 0
Global health status/quality of life score of the FACT-M subscale - Patient's health-related quality of life
Timepoint [6] 0 0
Up to 60 days post progression (5 years)
Secondary outcome [7] 0 0
Global health status/quality of life score of the EQ-5D-5L - Patient's health-related quality of life
Timepoint [7] 0 0
Up to 60 days post progression (5 years)
Secondary outcome [8] 0 0
Time to 10 point definitive deterioration in overall quality of life score from EORTC QLQ-C30 - Patient's health-related quality of life
Timepoint [8] 0 0
Up to 60 days post progression (5 years)
Secondary outcome [9] 0 0
PFS by PD-L1 expression - PFS analysis will be performed by PD-L1 subgroup (positive, negative) where a positive status is defined as having = 1% expression and a negative status is defined as having < 1% expression.
Additionally PD-L1 subgroups will also be assessed using defined by a PD-L1 expression level cut-off of 10%, where a positive status is defined as having = 10% expression and a negative status is defined as having < 10% expression.
Timepoint [9] 0 0
Up to disease progression or death due to any cause, whichever occurs first (5 years)
Secondary outcome [10] 0 0
OS by PD-L1 expression - OS analysis will be performed by PD-L1 subgroup (positive, negative) where a positive status is defined as having = 1% expression and a negative status is defined as having < 1% expression.
Additionally PD-L1 subgroups will also be assessed using defined by a PD-L1 expression level cut-off of 10%, where a positive status is defined as having = 10% expression and a negative status is defined as having < 10% expression.
Timepoint [10] 0 0
Up to disease progression or death due to any cause, whichever occurs first (5 years)

Eligibility
Key inclusion criteria
Inclusion criteria Part 1: Safety run-in

- Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation

- Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN

- ECOG performance status = 1

Part 2: Biomarker cohort

- Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation

- At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection

- ECOG performance status = 2

Part 3: Double-blind, randomized, placebo-controlled part

- Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation

- ECOG performance status = 2
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Part 1: Safety run-in

- Subjects with uveal or mucosal melanoma

- Any history of CNS metastases

- Prior systemic anti-cancer treatment for unresectable or metastatic melanoma

- Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6
month

- Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months

- Radiation therapy within 4 weeks prior to start of study treatment

- Active, known, suspected or a documented history of autoimmune disease

Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part

- Subjects with uveal or mucosal melanoma

- Clinically active cerebral melanoma metastasis

- Prior systemic anti-cancer treatment for unresectable or metastatic melanoma

- Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6
month

- Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months

- Radiation therapy within 4 weeks prior to start of study treatment

- Active, known, suspected or a documented history of autoimmune disease

Other protocol-defined Inclusion/Exclusion may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Gateshead
Recruitment hospital [2] 0 0
Novartis Investigative Site - North Sydney
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Novartis Investigative Site - Greenslopes
Recruitment hospital [4] 0 0
Novartis Investigative Site - Prahran
Recruitment hospital [5] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2290 - Gateshead
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
3181 - Prahran
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the safety and efficacy of the combination of an anti-PD-1 antibody
(Spartalizumab (PDR001)), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in
unresectable or metastatic BRAF V600 mutant melanoma
Trial website
https://clinicaltrials.gov/show/NCT02967692
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications